100 years of glucagon and 100 more – published online 27/06/2023

Nicolai J. Wewer Albrechtsen, Jens J. Holst, Alan D. Cherrington, Brian Finan, Lise Lotte Gluud, Danielle Dean, Jonathan E. Campbell, Stephen R. Bloom, Tricia M.-M. Tan, Filip K. Knop, Timo D. Müller

More than 100 years ago, scientists were on the path to discovering a central novel metabolic regulator, now known as glucagon. Although the role of glucagon in diabetes has been studied intensively, its place in physiology and pathophysiology is still debated. In this issue, Wewer Albrechtsen et al (https://doi.org/10.1007/s00125-023-05947-y) capture the fundamentals of glucagon biology and its role in metabolic diseases. Key questions on how glucagon secretion is controlled, not only by glucose but also by amino acids and lipids, are addressed. In addition, the authors discuss how a new concept, termed ‘glucagon resistance’, may explain the diabetogenic hyperglucagonaemia observed in metabolic diseases. The authors propose that future glucagon research may help to uncover the molecular backbone of inter-organ dysfunction in individuals with diabetes and liver disease. They conclude that, as well as treating hypoglycaemia, glucagon-based therapies may also provide benefits for weight loss and the treatment of fatty liver disease. The figures from this review are available as a downloadable slideset

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